Molecular mechanisms of AMPA receptor synapse formation

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Brain cells (neurons) transmit electrical information through the central nervous system and elicit specific behaviors through specialized connections called synapses. During development, the intricate and precise pattern of neuronal synapse connections is formed. The goal of this project is to understand the mechanism by which a novel protein (SynDIG1) that was identified in the Principal Investigator's (PI) laboratory functions in synapse development. This study will test the hypothesis that SynDIG1 anchors AMPA-type glutamate receptors (AMPA-Rs) at the postsynaptic compartment via interaction with scaffolding proteins. The researchers will use a combination of approaches including biochemistry, immunocytochemistry, and electrophysiology to address this possibility. While significant progress has been made in the field regarding presynaptic differentiation such as synaptic vesicle clustering and postsynaptic recruitment of scaffolds and NMDA-type glutamate receptors (NMDA-Rs), less is known about the molecules implicated in AMPA-R recruitment during synapse development. Thus, the results of the proposed experiments will fill a major gap in the field of synapse development and function. The broader impacts of the proposed studies include integration of the research and education activities of the PI, specifically in the context of broadening the participation of undergraduate students from underrepresented groups (primarily Hispanic/Latino). The PI is an active participant in various campus programs aimed to increase the number of underrepresented students pursuing postgraduate degrees in science; thus, the PI is in a strong position to recruit such students to the laboratory as members of the research team for this project. Undergraduate participation will be directed by the PI in conjunction with graduate students in the laboratory, thereby integrating research, teaching, and scientific community outreach activities for students pursuing graduate studies in the laboratory.